Study of Adding Cetuximab to Chemotherapy for the Treatment of Advanced and/or Recurrent Cervical Cancer (MITO CERV 2)

Randomized Phase II Study of Carboplatin and Paclitaxel +/- Cetuximab, in Advanced and/or Recurrent Cervical Cancer

This study aims to assess the activity of a combination of cetuximab (weekly) with carboplatin + paclitaxel (every three weeks) comparing it to chemotherapy alone in terms of event-free survival (EFS).

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: paclitaxel; Drug: carboplatin; Drug: cetuximab

Detailed Description

The poor long-term results in the standard treatment of chemotherapy for cervical cancer make research into new, more beneficial treatment strategies necessary. Cetuximab is a new type of drug that blocks the epidermal growth factor receptor (anti-EFGR), and has shown significant activity in other cancers (colon, head and neck) where expression of EGFR is high. Cervical cancer cells express EGFR in a very high proportion of cases, especially in recurrent or resistant disease. This study evaluates the activity of the addition of cetuximab to full doses of carboplatin and paclitaxel.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Brindisi, Italy
    • Ospedale Senatore Antonio Perrino
  • Cagliari, Italy
    • Ospedale Oncologico A. Businco
  • Campobasso, Italy
    • Universita Cattolica del Sacro Cuore
  • Meldola, Italy
    • Istituto Romagnolo per lo Studio e la Cura dei Tumori
  • Milano, Italy
    • Istituto Nazionale Tumori
  • Modena, Italy
    • A.O. Unversitaria Policlinico
  • Napoli, Italy, 80131
    • Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico
  • Napoli, Italy
    • A.O. Universitaria Federico II
  • Napoli, Italy
    • Seconda Universita di Napoli
  • Padova, Italy
    • Istituto Oncologico Veneto
  • Perugia, Italy
    • Ospedale Silvestrini
  • Roma, Italy
    • Istituto Regina Elena
  • Roma, Italy
    • Universita Cattolica del Sacro Cuore
  • Trento, Italy
    • Ospedale S. Chiara
  • Udine, Italy
    • A.O. di Udine S. Maria della Misericordia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Advanced and/or metastatic cervical cancer patients untreated or having failed only one previous chemotherapy (with at least 6 months of progression free interval, with or without concomitant or sequential radiotherapy).
• At baseline, presence of at least one measurable target lesion (a lesion that can be accurately measured in at least one dimension i.e. longest diameter at least 20 mm with conventional CT scan or at least 10 mm with spiral CT scan according to RECIST Criteria).
• Not amenable to surgery and/or radiotherapy.
• PS 0-1 according to ECOG.
• Age >18.
• Life expectancy of at least 3 months.

• Adequate organ functions

  • Hematopoietic: Leukocytes > 3,000/mm3; Absolute neutrophil count > or = 1,500/mm3; Platelets count > or = 100,000/mm3; Hemoglobin > or = 9 g/dL

  • Hepatic: AST and ALT < or = 3 times upper limit of normal (ULN)*; Alkaline phosphatase < or = 3 times ULN*; Bilirubin < or = 1.5 times ULN

    *: < or = 5 times ULN if liver metastases are present

  • Renal: Creatinine clearance > or = 45 mL/min
• No other invasive malignancy within the past 5 years except non-melanoma skin cancer.
• All radiology studies must be performed within 28 days prior to randomization.
• Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule.
• Written informed consent.

Exclusion Criteria:

• Pregnant (potentially fertile patients must use contraceptive measures to avoid pregnancy during and for at least 3 months after study participation and must have a negative serum pregnancy test at baseline).
• Patients should not be breast-feeding during treatment and for 2 months following the end of treatment.
• More than one previous chemotherapy line.
• Active infection requiring antibiotics.
• Symptomatic peripheral neuropathy >grade 2 according to the CTCAE.
• Congestive heart failure or angina pectoris even if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled high risk hypertension or arrhythmia.
• Known hypersensitivity to the study drugs or to drugs with similar chemical structures.
• Concurrent treatment with other experimental drugs.
• Participation in another clinical trial with any investigational drug within 30 days prior to study screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; chemotherapy plus cetuximab	Drug: paclitaxel; 175 mg/m2 IV day 1, every 21 days; Drug: carboplatin; AUC 5 IV day 1 every 21 days; Drug: cetuximab; 400 mg/m2 IV, one week before starting carboplatin and paclitaxel; then 250 mg/m2 IV day 1, weekly
Active Comparator: Arm B; chemotherapy	Drug: paclitaxel; 175 mg/m2 IV day 1, every 21 days; Drug: carboplatin; AUC 5 IV day 1 every 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
event free survival	after 3 and 6 cycles of treatment (each cycle is 21 days), and every 3 months thereafter up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival		18 months
EGFR/KRAS expression and correlation with cetuximab activity		at 18 months
adverse events	according CTCAE criteria	after each treatment cycle (each cycle is 21 days) up to 30days
skin toxicity and correlation with cetuximab activity		after 3 and 6 cycles of therapy (each cycle is 21 days), and every 3 months thereafter up to 18 months

Collaborators and Investigators

• Sponsor: National Cancer Institute, Naples
• Investigators: Principal Investigator: Alessandro Morabito, M.D.,, National Cancer Institute, Naples; Principal Investigator: Sandro Pignata, M.D., Ph.D., National Cancer Institute, Naples; Principal Investigator: Francesco Perrone, M.D., Ph.D., National Cancer Institute, Naples; Principal Investigator: Ciro Gallo, M.D., Ph.D., University of Campania "Luigi Vanvitelli"

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 15, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (Estimated): October 16, 2009

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: chemotherapy; EGFR
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Carboplatin; Paclitaxel; Cetuximab
• Other Study ID Numbers: MITO CERV 2; 2009-010099-74 (EudraCT Number)